Mechanism of effect
Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.
Pharmacodynamic
No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion.
Pharmacokinetics
Protein Bound: 94-96%
Vd: 25 L
Half-Life: 40 min
Metabolism: CYP1A2 (low amount)
Time to peak (serum): At end of infusion
Excretion: Feces (90%); urine (1-10%)
Dosage
Adult
Chronic Lymphocytic Leukemia
100 mg/m² IV infusion on days 1 and 2 of 28-day cycle, repeated for up to 6 cycles
Dosage modifications
- Hematologic toxicity
- ≥Grade 3: Reduce dose to 50 mg/m² on Days 1 and 2
- If ≥grade 3 toxicity reoccurs, reduce dose to 25 mg/m² on Days 1 and 2
- Nonhematologic toxicity
- Clinically significant toxicity ≥grade 3: Reduce dose to 50 mg/m² on Days 1 and 2 of each cycle
- Dose re-escalation may be considered
Non-Hodgkin Lymphoma
120 mg/m² IV infusion on days 1 and 2 of 21-day cycle repeated for up to 8 cycles
Dosage modifications
- Hematologic toxicity
- Grade 4: Reduce dose to 90 mg/m² on Days 1 and 2 of each cycle
- If grade 4 toxicity recurs, reduce dose to 60 mg/m² on Days 1 and 2 of each cycle
- Non-hematologic toxicity
- ≥Grade 3: Reduce dose to 90 mg/m² on Days 1 and 2 of each cycle
- If toxicity ≥grade 3 reoccurs, reduce dose to 60 mg/m² on Days 1 and 2 of each cycle
Pediatric
Safety and efficacy not established
Drug contraindications
palpitations , atrial fibrillation , Myocardial Infarction , Congestive Heart Failure , severe hypersensitivity reactionsSide effects
depression , Anxiety , Pain , Insomnia , Diarrhea , Headache , weight decrease , nausea , chest pain , dry mouth , vomiting , vertigo , Dyspnea , asthenia , Peripheral edema , Cough , fever , anorexia , Arthralgia , Upper respiratory tract infection , Hyperbilirubinemia , itching , tiredness , Abdominal pain , Leukopenia , thrombocytopenia , Rash , Hypocalcemia , Febrile NeutropeniaInteractions
Zileuton , Varicella-Zoster Vaccines , thiotepa , Infliximab , Deferiprone , Fingolimod , Natalizumab , Clozapine , Influenza vaccine , Palifermin , Golimumab , Baricitinib , rotavirus vaccine , Adalimumab , Certolizumab , Measles vaccine , Rubella Vaccines , Mumps vaccine , Tofacitinib , Meningococcal conjugate vaccineAlerts
Interrupt if severe infusion reactions
Mild-mod renal impairment, mild hepatic impairment
Possibility of anaphylactic/infusion reactions: severe in rare cases
Myelosuppression may occur; delay or reduce dose; restart treatment based on ANC and platelet count recovery; complications of myelosuppression may lead to death
Monitor for fever and other signs of infection and treat promptly
Severe infusion and anaphylactic reactions reported; monitor clinically and discontinue therapy; premedicate in subsequent cycles for milder reactions
Tumor lysis syndrome reported; acute renal failure and death may occur; anticipate and use supportive measures
Fatal and serious skin reactions have been reported with bendamustine treatment in clinical trials and postmarketing safety reports, including toxic skin reactions [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema, and rash; events occurred when given as a single agent and in combination with other anticancer agents or allopurinol; monitor patients with skin reactions closely; if skin reactions are severe or progressive, withhold or discontinue bendamustine hydrochloride injection
Premalignant and malignant diseases reported
Tumor lysis syndrome reported with use; onset tends to be within first treatment cycle of bendamustine hydrochloride and, without intervention, may lead to acute renal failure and death; preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels
Fatal and serious cases of liver injury reported with bendamustine hydrochloride injection
Monitor liver chemistry tests prior to and during treatment
Erythema and maked swelling can occur with extravasation; assure good venous access and monitor infusion site during and after administration
Fetal harm can occur when administered to a pregnant woman; women should be advised to avoid becoming pregnant when receiving bendamustine
Increased risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster; patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration
Points of recommendation
- Tell all of your health care providers that you take bendamustine. This includes your doctors, nurses, pharmacists, and dentists.
- Avoid driving and doing other tasks or actions that call for you to be alert until you see how bendamustine affects you.
- Have blood work checked as you have been told by the doctor. Talk with the doctor.
- If you smoke, talk with your doctor.
- This medicine may lower the ability of your bone marrow to make blood cells that your body needs. This can lead to needing a blood transfusion and very bad and sometimes deadly bleeding problems or infections. Tell your doctor right away if you have signs of infection like fever, chills, or sore throat; any bruising or bleeding; or if you feel very tired or weak.
- You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
- You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
- Very bad and sometimes deadly liver problems have happened with bendamustine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
- Heart problems like heart failure have happened in people taking bendamustine. Sometimes, this has been deadly. Call your doctor right away if you have chest pain or pressure, a heartbeat that does not feel normal, shortness of breath, a big weight gain, or swelling in the arms or legs.
- A very bad and sometimes deadly reaction has happened with bendamustine. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
- If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 3 months after care ends. Use birth control that you can trust.
- If you are a man and your sex partner gets pregnant while you take bendamustine or within 3 months after your last dose, call your doctor right away.
- This medicine may affect sperm in men. This may affect being able to father a child. Talk with the doctor.
- This medicine may cause harm to the unborn baby if you take it while you are pregnant.
- Use birth control that you can trust to prevent pregnancy while taking bendamustine and for 3 months after care ends.
- If you get pregnant while taking bendamustine or within 3 months after your last dose, call your doctor right away.
- If you have upset stomach, throwing up, diarrhea, or are not hungry, talk with your doctor. There may be ways to lower these side effects.
- Talk with your doctor before getting any vaccines. Use of some vaccines with bendamustine may either raise the chance of an infection or make the vaccine not work as well.
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